Variant 5-172683443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142651.3(NEURL1B):c.602C>T(p.Thr201Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,295,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

NEURL1B
NM_001142651.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17506391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NEURL1B	NM_001142651.3 linkuse as main transcript	c.602C>T	p.Thr201Met	missense_variant	3/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2 linkuse as main transcript	c.56C>T	p.Thr19Met	missense_variant	2/4		NP_001295106.1
NEURL1B	NM_001308178.2 linkuse as main transcript	c.578-2728C>T		intron_variant			NP_001295107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEURL1B	ENST00000369800.6 linkuse as main transcript	c.602C>T	p.Thr201Met	missense_variant	3/5	1	NM_001142651.3	ENSP00000358815.5	A8MQ27-1
NEURL1B	ENST00000522853.5 linkuse as main transcript	c.56C>T	p.Thr19Met	missense_variant	2/4	1		ENSP00000430001.1	A8MQ27-2
NEURL1B	ENST00000520919.5 linkuse as main transcript	c.578-2728C>T		intron_variant		1		ENSP00000429797.1	A8MQ27-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000232

AC:

AN:

1295684

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

636974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000475

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000144

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.67e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.602C>T (p.T201M) alteration is located in exon 3 (coding exon 3) of the NEURL1B gene. This alteration results from a C to T substitution at nucleotide position 602, causing the threonine (T) at amino acid position 201 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.070

Eigen_PC

Benign

0.0062

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.64

.;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.048

Sift

Uncertain

0.015

D;T

Sift4G

Uncertain

0.047

D;T

Polyphen

0.93

.;P

Vest4

0.11

MutPred

0.33

.;Loss of phosphorylation at T201 (P = 0.0418);

MVP

0.42

MPC

0.72

ClinPred

0.32

GERP RS

3.8

Varity_R

0.075

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over